Hepatic fibrosis. Hepatic fibrosis (liver fibrosis) is a wound healing response characterized by the excessive accumulation of scar tissue (i.e. extracellular matrix) in the liver. Normal structural elements of tissues are replaced with excessive amounts of non-functional scar tissue. Needle liver biopsy is the primary tool for the diagnosis and assessment of fibrosis yet there are a number of well-documented limitations and disadvantages to this technique including patient discomfort, pain, bleeding, and death in rare cases. Furthermore, a biopsy can be unreliable if fibrosis is not homogenous throughout the liver. Hepatic fibrosis can be caused by various factors including alcohol and viruses.
Cirrhosis. Hepatic cirrhosis is the most severe form of liver scarring and, unlike hepatic fibrosis, is generally considered to be irreversible and nodular. Cirrhosis is the cause of over 6000 deaths every year in the UK and approximately 27,000 in the USA, making it the ninth leading cause of death (MacSween et al., (2002), Pathology of the Liver, 4th Edition, Churchill Livingstone). Cirrhosis is a major risk factor for HCC and, at this stage of liver cancer, the only curative approach is liver transplantation. In the case of virally induced liver cancer, hepatic scarring and HCC can recur after transplantation. It is imperative to diagnose fibrosis in the early stages of reversible liver scarring so that irreversible cirrhosis can be prevented.
Hepatitis C virus. Approximately 170 million people worldwide, i.e. 3% of the world's population (see e.g. WHO, J. Viral. Hepat. 1999; 6: 35-47), and approximately 4 million people in the United States are infected with Hepatitis C virus (HCV, HepC). HCV is of the leading causes of hepatic fibrosis and cirrhosis. About 80% of individuals acutely infected with HCV become chronically infected. Hence, HCV is a major cause of chronic hepatitis. Once chronically infected, the virus is almost never cleared without treatment. In rare cases, HCV infection causes clinically acute disease and even liver failure. Chronic HCV infection can vary dramatically between individuals, where some will have clinically insignificant or minimal liver disease and never develop complications and others will have clinically apparent chronic hepatitis and may go on to develop fibrosis and cirrhosis. About 20% of individuals with HCV who do develop cirrhosis will develop end-stage liver disease and have an increased risk of developing primary liver cancer.
There is a need for improved methods of diagnosing hepatic fibrosis and cirrhosis in patients